Background:The area of e-Health is broad and has an excellent growth potential. An increasing number of experts believe that e-Health will fuel the next breakthroughs in health system improvements throughout the world, but there is frequent evidence of unsustainable use of e-Health systems in medical centres, particularly hospitals, for different reasons in different countries. Iran is also a developing country which is presently adopting this promising technology for its traditional healthcare delivery but there is not much information about the use of e-Health systems in its hospitals, and the weakness and opportunities of utilization of such Hospital Information Systems (HIS).Methods:For this research, a number of Hospitals from Isfahan, Iran, are selected using convenient sampling. E-health research professionals went there to observe their HIS and collect required data as a qualitative survey. The design of interview questions was based on the researchers’ experiences and knowledge in this area along with elementary interviews with experts on HIS utilization in hospitals.Results:Efficient administration of e-health implementation improves the quality of healthcare, reduces costs and medical errors, makes healthcare resources available to rural areas, etc. However, there are numerous issues affecting the successful utilization of e-health in Hospitals, such as a lack of a perfect HIS implementation plan and well-defined strategy, inadequate IT-security for the protection of e-health-related data, improper training and educational issues, legal challenges, privacy concerns, improper documentation of lessons learned, resistance to the application of new technologies, and finally a lack of recovery plan and disaster management. These results along with some informative stories are extracted from interview sessions to uncover associated challenges of HIS utilization in Iranian hospitals.Conclusion:The utilization of e-health in Iranian hospitals, particularly those in Isfahan, is subject to several challenges and there is no proper long-term strategy plans for HIS initiation, development, and improvement in Iranian hospitals. In order to address these problems, six recommendations are provided. Hence, human resource and e-health professionals from third party consultancy companies along with medical university scholars have to assist such hospitals to undertake the proposed solutions in order to provide proper plans to overcome future challenges and have a mature HIS in accordance with expected HIS utilization from hospitals and medical universities.